CD16A 和 CD32 Fcγ 受体多态性与梅尼埃病中的循环免疫复合物：一项病例对照研究。
Polymorphisms of CD16A and CD32 Fcγ receptors and circulating immune complexes in Ménière's disease: a case-control study.
机构信息
Otology & Neurotology Group CTS495, Department of Otolaryngology, Hospital de Poniente, El Ejido, Almería, Spain.
出版信息
BMC Med Genet. 2011 Jan 5;12:2. doi: 10.1186/1471-2350-12-2.
BACKGROUND
Autoimmune diseases with elevated circulating autoantibodies drive tissue damage and the onset of disease. The Fcγ receptors bind IgG subtypes modulating the clearance of circulating immune complexes (CIC). The inner ear damage in Ménière's disease (MD) could be mediated by an immune response driven by CIC. We examined single-nucleotide polymorphism (SNPs) in the CD16A and CD32 genes in patients with MD which may determine a Fcγ receptor with lower binding to CIC.
METHODS
The functional CD16A (FcγRIIIa559A > C, rs396991) and CD32A (FcγRIIa519A > G, rs1801274) SNPs were analyzed using PCR-based TaqMan Genotyping Assay in two cohorts of 156 mediterranean and 112 Galicia patients in a case-control study. Data were analyzed by χ2 with Fisher's exact test and Cochran-Armitage trend test (CATT). CIC were measured by ELISA for C1q-binding CIC.
RESULTS
Elevated CIC were found in 7% of patients with MD during the intercrisis period. No differences were found in the allelic frequency for rs396991 or rs1801274 in controls subjects when they were compared with patients with MD from the same geographic area. However, the frequency of AA and AC genotypes of CD16A (rs396991) differed among mediterranean and Galicia controls (Fisher's test, corrected p = 6.9 × 10-4 for AA; corrected p = 0.02 for AC). Although genotype AC of the CD16A receptor was significantly more frequent in mediterranean controls than in patients, [Fisher's test corrected p = 0.02; OR = 0.63 (0.44-0.91)], a genetic additive effect for the allele C was not observed (CATT, p = 0.23). Moreover, no differences were found in genotype frequencies for rs396991 between patients with MD and controls from Galicia (CATT, p = 0.14). The allelic frequency of CD32 (rs1801274) was not different between patients and controls either in mediterranean (p = 0.51) or Galicia population (p = 0.11).
CONCLUSIONS
Elevated CIC are not found in most of patients with MD. Functional polymorphisms of CD16A and CD32 genes are not associated with onset of MD.
背景
自身免疫性疾病伴有循环自身抗体升高可导致组织损伤和疾病发作。Fcγ 受体结合 IgG 亚型，调节循环免疫复合物（CIC）的清除。梅尼埃病（MD）的内耳损伤可能是由 CIC 驱动的免疫反应介导的。我们检测了 MD 患者中 CD16A 和 CD32 基因的单核苷酸多态性（SNP），这些 SNP 可能决定了与 CIC 结合能力较低的 Fcγ 受体。
方法
采用基于 PCR 的 TaqMan 基因分型检测法，在 156 名地中海和 112 名加利西亚 MD 患者的病例对照研究中分析了功能性 CD16A（FcγRIIIa559A>C，rs396991）和 CD32A（FcγRIIa519A>G，rs1801274）SNP。采用卡方检验和 Cochran-Armitage 趋势检验（CATT）分析数据。采用 ELISA 法检测 C1q 结合 CIC 来测量 CIC。
结果
在疾病缓解期，7%的 MD 患者发现 CIC 升高。在来自同一地理区域的 MD 患者与对照者相比，rs396991 或 rs1801274 的等位基因频率无差异。然而，地中海和加利西亚对照组的 CD16A（rs396991）AA 和 AC 基因型的频率不同（Fisher 检验，校正后 p = 6.9×10-4 为 AA；校正后 p = 0.02 为 AC）。虽然地中海对照组 CD16A 受体的 AC 基因型明显高于患者（Fisher 检验校正后 p = 0.02；OR = 0.63（0.44-0.91）），但等位基因 C 的遗传累加效应并未观察到（CATT，p = 0.23）。此外，MD 患者与加利西亚对照组 rs396991 基因型频率无差异（CATT，p = 0.14）。CD32（rs1801274）的等位基因频率在 MD 患者和地中海（p = 0.51）或加利西亚人群（p = 0.11）的对照组之间也无差异。
结论
大多数 MD 患者中未发现 CIC 升高。CD16A 和 CD32 基因的功能性多态性与 MD 的发病无关。
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